Visna is a slow progressive demyelinating disease of the central nervous system of sheep caused by a virus which shares many biological properties with the RNA tumor virus. The proposed research will examine (a) the mechanisms of persistence of virus, (b) the pathogenesis of the demyelinating lesions in the brain and spinal cord, and (c) the effects of altered host immune competence on the outcome of infection. The study will be divided into three parts: (1) short-term studies in infected young adult lambs, (2) long-term studies in the same group of animals, and (3) infection of thymectomized fetal lambs. On the basis of pilot experiments, studies will be directed to: (a) Identification of infected cells using virologic techniques both at the cellular and molecular levels, histochemical tests including immunofluorescence, immunoperoxidase, and autoradiography and electron microscopy. (b) The lymphoproliferative aspect of the disease using virologic and a variety of immunological techniques. (c) The humoral and cellular immune responses to the infection and the pathological effects, or lack of, in infected immunologically compromised lambs.